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IBBM PBMS (Specialist)IBBM PBMS (Specialist)IBBM PBMS (Specialist)IBBM PBMS (Specialist)Basic Blood & Physiology ReviewBasic Blood & Physiology ReviewBasic Blood & Physiology ReviewBasic Blood & Physiology Review

Keith Samolyk CCP Emeritus

October 21st 2017

Q & O Meeting Portland OR

ETHICS OF BLOOD MANAGEMENTETHICS OF BLOOD MANAGEMENTETHICS OF BLOOD MANAGEMENTETHICS OF BLOOD MANAGEMENT

-First Do No Harm “Primum Non Nocere”

-Transfuse only when Absolutely Necessary

-Transfuse Only what’s Required and Sparingly

- Use the Freshest Blood Components Possible

- Minimal Sampling “Blood Draws” (Peds Tubes if poss)

-Avoid Waste/ Recover as much Autologous as possible

-Use POC Labs to Justify Transfusions

-Use Evidence Based Medicine to Guide Decisions

-It’s not Blood Management… It’s Fluid Management!

- NEJM Oct 2017 “Crisis in the Sustainability of the U.S. Blood System”

H Klein NIH

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***Multidisciplinary Approach***“PEOPLE IN THE CHAIN”

Door to Door HemovigilanceOr it Doesn’t Work at All !

Primary Doctor

Cardiologist

Admission Care Team

Anesthesia

Surgeon

Perfusion

ICU Care Team, Nurses Hospital Wide

Administrators

It only takes 1 weak Link in the Chain And a Patient is then Exposed to “Donor”

Allogeneic Blood Products!

Hawk-like Multidisciplinary Teamwork is the ONLY Way it Works

Treat every Patient like a JW with a Small BSA for Best Practice Outcomes!

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To Start What is Blood?

Whole Blood

Red Cells

White Cells

Platelets

Plasma

Hemoglobin

Hematocrit

Interleukins

Salts, Sugars,

Hormones, Vitamins, Enzymes, Minerals,

etc.

Interferons

Foundation

of

Hemostasis

Clotting Factors

Proteins

-COP- Albumin,

Globulins,

etc.

Fibrinogen Factors:

VII, VIII, IX, X, etc.

TThhee BBiigg PPiiccttuurree ooff WWhhoollee BBlloooodd

Protection

Wound Healing

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The 4 Major Components of BloodThe 4 Major Components of BloodThe 4 Major Components of BloodThe 4 Major Components of Blood

Norm Hct WBC Norm

36-50 % 4-10 K

Hgb Norm

12-17 g/dl

Life Span

120 days

Life Span

9-12 Days

Norm Ptl # Fib Norm

140-400K 150-400mg/dl

3rd in Spleen

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Systemic and Pulmonary Circulation Around

the body to the Organ Systems

Where the Volume Goes and Under what

Pressure, “Everything is Hydrokinetic”

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Arteries to Veins

VASCULAR ANATOMY

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But This is!

Where the Rubber Meets the Road

What is Microcirculation?

Microcirculation deals with the flow of blood from arterioles to capillaries or sinusoidsto venules. Blood flows freely between an arteriole and a venule through a vessel channel called a thoroughfare channel. Capillaries extend from this channel and structures called precapillary sphincters control the flow of blood between the arteriole and capillaries.

The precapillary sphincters contain muscle fibers that allow them to contract. When the sphincters are open, blood flows freely to the capillary beds where gases, nutrients and waste can be exchanged with body tissue. When the sphincters are closed, blood is not allowed to flow through the capillary beds and flows directly from the arteriole to the venule through the thoroughfare channel.

It is important to note that blood is supplied to all parts of the body at all times but all capillary beds do not contain blood at all times. Blood is diverted to the parts of the body that need it most at a particular time. For ex. when you eat a meal blood is diverted from other parts of your body to the digestive tract, or the Fight or Flight response ie: Tiger! CO = 5 lpm to 20 lpm

Vessel Sizes

Vessel Diameter in Microns

Arterioles 20-50

Capillaries 5-10

Sinusoids 30-40

Venules 30-40

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What Sizes

Arterioles

Small precapillary resistance vessels (10-50 µ) composed of an

endothelium surrounded by one or more layers of smooth muscle.

Richly innervated by sympathetic adrenergic fibers and highly

responsive to sympathetic vasoconstriction via both a 1 and a 2

post junctional receptors. Represent the major site for regulating

SVR systemic vascular resistance (***Vascular Tone***).

Primary function within an organ is flow regulation, thereby

determining oxygen delivery and the washout of metabolic by-

products. Regulated, in part, capillary hydrostatic pressure and

therefore influences capillary fluid exchange.

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Vaso-Action of the Arterioles in Regulating SVR

***Norm= 800-1200d/cm2***

Hypotension is NOT always Hypovolemia! (No Heavy Handed Fluids)

Push the SVR not the Starling Curve! normal 800-1200.

Hemodilution is the Enemy! It leads to Organ Edema and Organ

Dysfunction that leads to Morbidity and Mortality!

HD creates to a Dilutional Anemia and a Dilutional Coagulopathy that leads

to Blood Products and that leads to M&M!

Give as little Volume as necessary and keep the SVR High Normal if possible

Anesthesia Can Really

Help out a lot Here!

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What are capillaries?

Capillaries walls are thin and are composed of endothelium (a single layer of overlapping flat cells). Oxygen, carbon dioxide, nutrients and wastes are exchanged through the thin walls of the capillaries.

The flow of blood is controlled by structures called precapillary sphincters. These structures are located between arterioles and capillaries and contain muscle fibers that allow them to contract. When the sphincters are open, blood flows freely to the capillary beds of body tissue. When the sphincters are closed, blood is not allowed to flow through the capillary beds

Image courtesy of Carolina Biological Supply/Access

Excellence

Capillary Size

Capillaries are so small that red blood cells can only travel through them in single file.

•5-10 microns in diameter.

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Hct 40%

Hct23%

Normal Hct = 40+/-%

For Every 1000 mLsof Crystalloid Fluid

Given to Patients

Only 200-300 mLs will remain Intravascular in 30-45 mins

Dilution leads to organ dysfunction and a coagulopathy

Chappell Fluid Article: Trauma patient study by Lowell et. al.

Hemodiluted Hct = +/- 23%

Tonicity of Fluids

• Osmolarity

• Ions (osmotic force)

• Proteins (oncotic force)

• Hypotonic

• Cells placed in a hypotonic solution swell

• Isotonic

• Hypertonic

• Cells placed in a hypertonic solution shrink

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Oncotic States

ALBUMIN IS IMPORTANT

Albumin is derived from adult human plasma. It is an oncotic protein in normal blood

serum concentrations of 3.6- 5.2 g/ dl that contributes to a normal colloidial osmotic

pressure COP of > 20 Torr. Levels below 3.2 gdl are generally considered dangerous

Serum albumin is increased in dehydration, and decreased in malnutrition, chronic liver

disease, malabsorption, nephrotic syndrome, SLE, burns. Is a Function of Nutrition.

During extracorporeal circulation a cardiovascular perfusion related phenomenon of

"third spacing" a condition where extracellular water migrates into the interstitial

spaces presents itself.

When third spacing is identified, e.g. fluid balances, low protein levels, additional

Albumin may be administered to regain fluid lost to the interstitum.

When injected intravenously, 50 mL of 25% albumin draws approximately 175 mL of

additional fluid into the circulation within 15 minutes, except in the presence of

marked dehydration.

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Albumin Albumin Albumin Albumin –––– Physiological rolePhysiological rolePhysiological rolePhysiological role

• Major functions

• Most abundant protein in plasma (69 kDa)

• +/- 80% of plasma colloid osmotic pressure

Normal COP is 18-22 mmHg (and Hemodilution really drops it)

• Transport and sequestration of bilirubin

• Transport of fatty acids, hormones, vitamins, enzymes, drugs (Warfarin, Diazepam, Digoxin, NSAIDS, Midazolam, Thiopental and others)

• Antioxidant and Free Radical Scavenger

• Inhibit Endothelial Cell Apoptosis and influences the Microcirculation by modifying the capillary permeability “by Protecting the Glycocalyx”

• Buffer in Acid Base Balance (as it fixes to H+ ions)

• No Maximal Dose and has No Effect on Hemostasis

gm/dl mmHg % of COP

Albumin 4.50 21.80 78%

Globulins 2.50 6.00 21%

Fibrinogen 0.30 0.20 1%

Total 7.30 28.00 100%

Plasma Protein Effects on Total

Colloid Osmotic Pressure

Plasma Proteins: The Key Elements of COP

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Edema: Most common clinical manifestation of an

Imbalance of forces at the capillary wall

Excess accumulation of fluid in the interstitial space that has not been

readsorbed into capillaries or taken up by the lymphatics

The 4 Causes of Edema include

• Obstruction

• Permeability or change in reflection coefficient

Increased protein permeability results in an imbalance

• Occurs in trauma, thermal injury, inflammation

• Life threatening manifestations - endotoxic shock, ARDS

• Plasma Proteins

• Reduction in circulating plasma proteins, esp Albumin• Liver dysfunction, malnutrition, or acute alteration of fluid status

• Albumin attenuates extravasation of fluid out of intravascular space

into the interstitial space

• Capillary pressure27

STARLINGS LAW

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The Microcirculation The Microcirculation The Microcirculation The Microcirculation

Daxor

Vascular Interstitial Lymphatic

Hydrostatic

Gradient

Osmotic

Gradient

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The Lymphatic

System

The Loss of Protein and Lymphatic Flow

Proteins

Lymph Flow

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The Lymphatic System Is a network of conduits that carry a clear fluid called lymph. It also includes the lymphoid

tissue that the lymph travels through. Lymphoid tissue is found in many organs,

particularly the lymph nodes, and in the lymphoid follicles associated with the digestive

system such as the tonsils. The system also includes all the structures dedicated to the

circulation and production of lymphocytes, which includes the spleen, thymus, bone

marrow and the lymphoid tissue associated with the digestive system.

The dissolved constituents of the blood do not directly come in contact with the cells and

tissues in the body, but first enter the interstitial fluid, and then the cells of the body.

Lymph is the fluid that is formed when interstitial fluid enters the conduits of the

lymphatic system. The lymph is not pumped through the

body like blood, it is moved predominately by the

contractions and movements of skeletal musclesThe lymphatic system has three interrelated functions. It is responsible for the removal of

interstitial fluid from tissues. It absorbs and transports fatty acids and fats as chyle to the

circulatory system. The last function of the lymphatic system is the production of

immune cells, such as lymphocytes, including antibody & producing monocytes. Diseases

and dysfunction/obstruction of the lymphatic system can cause swelling , edema and

other symptoms. Problems with the system can impair the body's ability to fight.

Fluid Overload is an Independent Predictor of Mortality

Chappell: A Rational Approach to Perioperative Fluid Management. Anesthesiology 2008: 109:723–40

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Clinicians can Reverse the Fluid Shifts that cause 3rd Spacing from Hemodilution and optimize the Patient’s Red Cell MassPatient’s Red Cell MassPatient’s Red Cell MassPatient’s Red Cell Mass, so that allogeneic blood products to treat a Dilutional Anemia and a Dilutional Coagulopathy can be minimized. *Extubate ASAP!Extubate ASAP!Extubate ASAP!Extubate ASAP!

ALBUMIN

Osmitrol

LASIX

Mannitol

HEMOCONCENTRATORS

Tools to Minimize Hemodilution

Chappell Fluid Article

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The Fluid Gate Keeper

The “Glycocalyx” the New Frontier

The Endothelial Glycocalyx, is a gel-like layer that coats the inner surface of the endothelium throughout the entire vascular tree less than 100nm thick

and is made up of negatively charged carbohydrate polymeric glycoproteins and

plasma soluble molecules produced by bacteria, epithelia and other protein cells.

Think of it as a non-stick Teflon coating on the luminal endothelial surfaces. The slime on the outside of a fish is actually considered to be a Glycocalyx.

The Glycocalyx layer contains very fine hair-like structures that contribute to cell-

cell recognition and transmit intracellular adhesion changes and shear forces to

the endothelium, ultimately regulating nitric oxide release, it consists of a wide

range of enzymes and proteins that regulate Leukocyte and Platelet adherence.

Its principal role in the vasculature is to maintain plasma and vessel wall homeostasis and equilibrium.

The Glycocalyx

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Glycocalyx has multiple functions: it mediates nitric oxide synthesis and superoxide

dysmutation, it acts as a protective "sieving" barrier, inhibits platelet adherence,

and coagulation, and it regulates inflammation by preventing leukocyte adhesion to the vessel walls.

One of its most important functions is to keep the endothelial wall responsive to

changes in vascular fluid dynamics within the vascular endothelium as it shields the vascular walls from direct exposure to blood flow shear stress, while serving as a vascular permeability barrier.

The Glycocalyx

A Non-Stick Coating Unless Disrupted

The Glycocalyx can get damaged from sheer stress decreasing NO availability,

increased oxidative stress, leakage of macromolecules, increased platelet

adherence, thrombin generation, and increased leukocyte adhesion, all of which set the stage for inflammation and thrombotic events. These damaged

Glycocalyx areas increase perivascular edema leading to a leakage of fluids and

proteins which causing tissue damage and loss of capillaries.

*Paper “Endothelial Glycocalyx and CPB” JECT Oct 2017 Myers & Wegner

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Its hypothesized that hypoxic perfusion of the Glycocalyx is sufficient enough to initiate a degradation mechanism of the endothelial barrier. Studies found that flow of oxygen throughout the blood vessels did not have to be completely absent (ischemic hypoxia), but that minimal levels of oxygen were sufficient enough to cause the degradation. Anesth Volume Loading Patient Reduces the Glycocalyx

Shedding of the Glycocalyx can be triggered by Fluid Shear Stress (FSS) ie the start up motion of an RBC in a tight capillary bed or the crushing passage of a WBC or Microbubble, and inflammatory stimuli such as Tumor necrosis factor (TNFa).

Whatever the stimulus, shedding of the Glycocalyx leads to a drastic increase in vascular permeability. This permeability enabling the passage of macromolecules and other harmful antigens leading to 3rd spacing, edema, organ edema and dysfunction. So it’s Really Important to Protect it!

Glycocalyx Shedding = Vascular Permeability.

Normal Abnormal

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APATHYAPATHYAPATHYAPATHYApathy is a state of indifference, or the

suppression of emotions such as concern,

excitement, motivation and passion. An

apathetic individual has an absence of

interest or concern to emotional, social,

or physical life. Don’t be Apathetic…

Change the Paradigm at your Institution.

Be The Leader in Blood Management!

Remember Hemodilution leads to Edema & Blood Products! Remember Hemodilution leads to Edema & Blood Products! Remember Hemodilution leads to Edema & Blood Products! Remember Hemodilution leads to Edema & Blood Products! And If its not yours its an “Organ Transplant” And If its not yours its an “Organ Transplant” And If its not yours its an “Organ Transplant” And If its not yours its an “Organ Transplant” with with with with Consequences! Consequences! Consequences! Consequences!

Do your best to avoid heavy handed Do your best to avoid heavy handed Do your best to avoid heavy handed Do your best to avoid heavy handed HemodilutionHemodilutionHemodilutionHemodilution!!!!Your decisions effect the patient for the rest of their life! Your decisions effect the patient for the rest of their life! Your decisions effect the patient for the rest of their life! Your decisions effect the patient for the rest of their life!

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Thank you for your time!Thank you for your time!Thank you for your time!Thank you for your time!